Tirzepatide vs. Semaglutide: What the SURMOUNT-5 Head-to-Head Trial Found
Medically reviewed by Lauren Orta, FNP-C.
In the SURMOUNT-5 head-to-head trial, people on tirzepatide lost more weight on average than people on semaglutide: about 20% vs about 14% of body weight at 72 weeks.
This article walks through the N Engl J Med (2025) paper in plain English: what was studied, what changed, what the limits are, and what it does not prove. Full citation and DOI link are at the end, with a PubMed record.
What the study found
SURMOUNT-5 was a 72-week, open-label phase 3b trial. It randomly assigned 751 adults with obesity, but without type 2 diabetes, to weekly tirzepatide (10 or 15 mg, the highest dose each person could tolerate) or weekly semaglutide (1.7 or 2.4 mg). The main question was simple: which one leads to more weight loss?
Average weight change at 72 weeks was -20.2% with tirzepatide and -13.7% with semaglutide. Waist size dropped 18.4 cm (about 7 inches) vs 13.0 cm (about 5 inches). People on tirzepatide were also more likely to reach 10%, 15%, 20% and 25% weight loss. Stomach side effects were the most common problem in both groups, mostly mild to moderate and mostly while doses were going up.
Key finding (from the study record): Weight -20.2% (tirzepatide) vs -13.7% (semaglutide) at 72 weeks; waist -18.4 cm vs -13.0 cm.
How the study was done
- Design: Phase 3b, open-label randomized trial, 72 weeks
- Who was studied: 751 adults with obesity, no type 2 diabetes
- Journal / year: N Engl J Med (2025)
- First author: Aronne LJ et al.
What it means — and what it does not
Useful takeaway: In this one trial, average weight loss was larger with tirzepatide than with semaglutide (about 20% vs about 14% of body weight). Individual results varied.
Limits and caveats: Open-label, so people knew which drug they were on. Funded by Eli Lilly, which makes tirzepatide. Brand-name drugs were tested; compounded versions are not FDA-approved and were not studied.
This evidence can inform a conversation with a licensed provider. It does not mean you will get the same results, and it is not a recommendation to start, stop, or change any medication on your own.
How this connects to care
AZTRT serves men in Arizona with telehealth evaluation, initial labs, and provider-guided plans when appropriate. AZTRT does not prescribe semaglutide; it appears here only as the comparison drug in this study. TRT plans are $149/month or $357/quarter with a 3-month minimum and include initial labs. Tirzepatide is a separate program. Compounded tirzepatide is not FDA-approved. AZTRT is cash pay only.
Relevant pages on this site:
FAQ
What did this study actually find?
Weight -20.2% (tirzepatide) vs -13.7% (semaglutide) at 72 weeks; waist -18.4 cm vs -13.0 cm. Design: Phase 3b, open-label randomized trial, 72 weeks. Who: 751 adults with obesity, no type 2 diabetes.
Does this mean I should start treatment?
No. Research informs care; it does not prescribe it. A licensed provider reviews your symptoms, labs, and history before any decision. Results vary.
What are the main limits of this evidence?
Open-label, so people knew which drug they were on. Funded by Eli Lilly, which makes tirzepatide. Brand-name drugs were tested; compounded versions are not FDA-approved and were not studied.
Is tirzepatide better than semaglutide for everyone?
No. This trial compared averages. Your provider looks at your health history, labs, side effects and goals. In this trial, both groups had meaningful average weight loss.
Keep reading
- How Do GLP-1 Medications Work? Tirzepatide Explained
- Building Sustainable Habits for Long-Term Weight Loss
- Setting Realistic Expectations for Your Health Journey
- The Connection Between Weight and Testosterone
- More on SURMOUNT-5: Tirzepatide vs Semaglutide, the Head-to-Head Trial
Reference
Aronne LJ et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med. 2025. https://doi.org/10.1056/NEJMoa2416394 · PubMed 40353578.
Next step
Book a free consult with an Arizona-licensed provider. Bring your questions — including anything this study raised for you.
Talk to a licensed provider. Results vary. Not medical advice.
Talk to a licensed provider. Results vary. Not medical advice.
